Delirium linked to tripled dementia risk in older adults, Australian study finds

In a recent study published in BMJ, researchers explored the relationship between delirium and new-onset dementia among older adults with no dementia diagnosis at baseline.

Study: Delirium and incident dementia in hospital patients in New South Wales, Australia: retrospective cohort study. Image Credit: LightField Studios/Shutterstock.com

Background

Delirium is a syndrome marked by inattention and loss of awareness, frequently caused by acute events such as sickness or surgery. It is frequent in hospitals, particularly among individuals of advanced age with serious medical problems.

Delirium is associated with adverse outcomes such as mortality, extended hospital admissions, and long-term cognitive deterioration.

A comprehensive review and meta-analysis reported an association of delirium with new-onset dementia among individuals without dementia; however, these studies had small sample sizes and did not account for the significant risk of mortality in this vulnerable population. As the worldwide dementia burden grows, it is critical to identify delirium’s modifiable risk factor.

About the study

The present study investigated whether delirium is associated with new-onset dementia in older adults using state-level hospital data linked to the New South Wales (NSW) Centre for Health Record Linkage.

The researchers conducted the study from July 2001 to March 2020, extracting data for 650,590 patients aged 65 years and older, excluding those with dementia at study initiation, as determined using the International Classification of Diseases, tenth revision (ICD-10) codes. They also excluded individuals with inconsistent data and those aged over 110 years.

The researchers matched delirium patients 1:1 to healthy individuals using clinical (e.g., diagnoses and procedures) and personal (e.g., gender, birth date, nationality, and residence) characteristics and followed them for over five years.

They considered the follow-up period as the duration between the index period (between January 2009 and December 2014) termination and that of the dataset.

They performed Fine-Gray hazards and Cox proportional hazards and modeling to determine the associations between delirium with mortality and new-onset dementia. Study covariates included age, HFRS scores, primary diagnosis, episode duration, and intensive care unit admission duration.

The team calculated hospital frailty risk scores (HFRS) and quantified the dose-response relationship between delirium and dementia incidence, stratifying data by sex.

They also performed sensitivity analyses by extending the landmark period from a year to two and repeating analyses after eliminating individuals who died or received a dementia diagnosis within two years of their index episode.

Results and discussion

The researchers analyzed 55,211 pairs of delirium and non-delirium individuals (48% male, mean age of 83 years). Among the participants, 63,929 (58%) died, and 19,117 (17%) developed incident dementia in the follow-up period.

Individuals with delirium showed a 39% increased risk of mortality [hazard ratio (HR), 1.4] and a three-fold higher risk for developing dementia (sub-distribution HR, 3.0) than non-delirium individuals.

Among patients who experienced at least one delirium episode in the landmark period, each additional delirium episode related to a 10% increased death risk (HR, 1.1).

The delirium-dementia association was more robust for males than females (sub-distribution HR, 3.2 vs. 2.9). Each additional delirium episode was related to a 20% higher new-onset dementia risk (sub-distribution HR, 1.2).

Sensitivity analyses yielded similar results, indicating the robustness of the primary findings. The persistent connection between delirium presence and new-onset dementia years after the delirium episode (and remission of the triggering stresses) indicated that delirium is more than just an epiphenomenon or a sign of undiagnosed dementia or a fragile brain.

Delirium and dementia have a dose-response association, which may lead to dementia through geriatric syndromes, medical consequences, and constraints. Delirium may potentially cause neuronal damage and neurodegeneration by disrupting biological systems.

The relationship between systemic inflammatory indicators, delirium, and dementia is multifaceted and impacted by dementia pathogenesis. Neuroinflammation indicators such as amyloid-beta (Aβ) and tau proteins are associated with both disorders.

The apolipoprotein (APOE) genotype has been linked to delirium, indicating a role for genetic profiles associated with systemic inflammation. Understanding the pathophysiological processes of delirium dementia may lead to the development of innovative therapies to prevent or slow neurodegeneration.

Conclusions

The study findings showed that delirium presence was significantly associated with dementia incidence among older individuals with no prior dementia diagnosis. Patients with delirium but without baseline dementia had a three-fold increased risk of developing dementia.

The findings indicate a causal link between the two disorders, necessitating the development of novel treatments. The study also emphasized the need to consider gender when examining the relationship between delirium and incident dementia. Delirium prevention and treatment can help lower the global dementia burden.

Men had a greater chance of incident dementia related to delirium, implying a poorer reserve of neuropathology. However, the relationship between neuropathological load and clinical dementia is non-linear, and there may be gender disparities in neuropathology patterns.

Men may have more severe delirium, and there may be underlying sex differences in the molecular underpinnings of delirium that cause brain destruction and hastened neurodegeneration. Future research should investigate these concepts to discover sex-specific intervention targets.